tbuckley/cabot-search huggingface dataset:
Versatile Hydrogel Dressings That Dynamically Regulate the Healing of Infected Deep Burn Wounds
Authors: Shihan Wang, Siwen Wu, Yuling Yang, Jiani Zhang, Yusi Wang, Rui Zhang, Li Yang
Journal: Advanced Healthcare Materials (2023)

Severe burns threaten patient lives due to pain, inflammation, bacterial infection, and scarring. Most burn dressings that are commonly used perform a single function and are not well suited for the management of deep burns. Therefore, a multifunctional antimicrobial peptide- and stem cell-loaded macroporous hydrogel that can fight bacterial infection and regulate wound healing progression by temporally regulating cytokine production by internal stem cells is developed. The macroporous skeletal hydrogel is manufactured via the cryogenic gelation of hyaluronic acid (cryogel). Based on the oxidative polymerization reaction of dopamine, the antimicrobial peptide DP7 is immobilized on the surface of the cryogel (DA7CG). Placental mesenchymal stem cells (PMSCs) are then packaged inside the macroporous hydrogel (DA7CG@C). According to the results of in vitro and in vivo experiments, during the inflammatory phase, DP7 inhibits infection and modulates inflammation; during the proliferative phase, DA7CG@C accelerates the regeneration of skin, blood vessels, and hair follicles via internal stem cells; and during the remodeling phase, DA7CG@C contributes to extracellular matrix remodeling due to the ability of DP7 to regulate the paracrine secretion of PMSCs, synergistically promoting scar-free healing. DA7CG@C can participate in all phases of wound healing; therefore, it is a promising dressing for burn treatment.
Mn<sup>2+</sup>/Ir<sup>3+</sup>‐Doped and CaCO<sub>3</sub>‐Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image‐Guided Synergistic Cancer Therapy
Authors: Shuaining Ma, Weiguo Xu, Yunwei Fei, Dan Li, Xiuna Jia, Jin Wang, Erkang Wang
Journal: Advanced Healthcare Materials (2023)

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.
When I use a word . . . Doing and non-doing
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The IndoEuropean root WERG, to do, gives us a workaday collection of work-related words, including “work” itself. The Greek derivative ἔργον gives a host of them, from ergodic to ergosphere, endergonic and exergonic reactions, hypergols and exergues, and numerous pharmacological actions designated as adrenergic, cholinergic, dopaminergic, GABAergic, histaminergic, monoaminergic, peptidergic, and purinergic. Surgeons’ work ethic is also evident in the name of their calling. Some, however, find work irksome or decide not to do it, either for no other reason than not wanting to, or because they have cause for going on strike, often pointing to complaints about remuneration or working conditions. The hospital consultants in England have recently joined the latter band, ostensibly complaining about pay, but equally, or even more so, because of the conditions of working in the NHS, which seems at last, after many years of deterioration, to have induced a fatal anergy in its staff.
An overview of infective endocarditis in the context of COVID-19 pneumonia
Authors: Ricardo Goncalves, Ruchika Meel
Journal:  (2023)

Abstract Infective endocarditis (IE) in the context of coronavirus disease (COVID-19) is an emerging clinical entity. If not identified timeously, it is associated with high morbidity and mortality. Herein, we provide an overview of the literature supported by a clinical vignette, and highlight the importance of early recognition and management of IE in the context of COVID-19 infection.
Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994
Authors: Gemma G. Kenter, Stefano Greggi, Ignace Vergote, Dionyssios Katsaros, Juliusz Kobierski, Heleen van Doorn, Fabio Landoni, Jacobus van der Velden, Nicholas Reed, Corneel Coens, Iske van Luijk, Nicoletta Colombo, Elzbietta van der Steen-Banasik, Nelleke Ottevanger, Antonio Casado, Annemarie Schratter-Sehn, Ignace Vergote, Jan Baptist Vermorken, Sevilay Altintas, Frederic Kridelka, Frédéric Goffin, Florence Joly-Lobbedez, Dionyssios Katsaros, Stefano Greggi, Nicoletta Colombo, Fabio Landoni, Paolo Zola, Annamaria Ferrero, Massimo Franchi, Nicoletta Donadello, Leon Massuger, Anca Ansink, Helena Van Doorn, Jacobus Van Der Velden, Rene Verheijen, W.M. van Baal, Gemma Kenter, Eleonora Van Dorst, Gemma Kenter, Katja Gaarenstroom, Gunnar Kristensen, Anna Kobierska, Julisz Kobierski, Carlos Freire de Oliveira, Cristina Frutuoso, Antonio Casado Herraez, Nicholas Reed, Rema Jyothirmayi, Andrew Nordin, Gordon Rustin
Journal: Journal of Clinical Oncology (2023)

The EORTC-55994 trial compared neoadjuvant chemotherapy (NACT) followed by radical surgery with concomitant chemoradiation (CCRT) in patients with Stage IB2-IIB cervical cancer. This trial took almost 12 years to recruit 626 patients with a median follow-up of 8.7 years.
Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study
Authors: Tara Sanft, Maura Harrigan, Courtney McGowan, Brenda Cartmel, Michelle Zupa, Fang-Yong Li, Leah M. Ferrucci, Leah Puklin, Anlan Cao, Thai Hien Nguyen, Marian L. Neuhouser, Dawn L. Hershman, Karen Basen-Engquist, Beth A. Jones, Tish Knobf, Anees B. Chagpar, Andrea Silber, Anna Tanasijevic, Jennifer A. Ligibel, Melinda L. Irwin
Journal: Journal of Clinical Oncology (2023)

Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy.
Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer
Authors: Luca Antonelli, Davide Ardizzone, Isamu Tachibana, Nabil Adra, Clint Cary, Lee Hugar, Wade J. Sexton, Aditya Bagrodia, Michal Mego, Siamak Daneshmand, Nicola Nicolai, Sebastiano Nazzani, Patrizia Giannatempo, Andrea Franza, Axel Heidenreich, Pia Paffenholz, Ragheed Saoud, Scott Eggener, Matthew Ho, Nathaniel Oswald, Kathleen Olson, Alexey Tryakin, Mikhail Fedyanin, Natacha Naoun, Christophe Javaud, Walter Cazzaniga, David Nicol, Axel Gerdtsson, Torgrim Tandstad, Karim Fizazi, Christian Daniel Fankhauser
Journal: Journal of Clinical Oncology (2023)

No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes.Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS).After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men.Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.
Diabetes: Doctors are told not to start new patients on GLP-1 agonists because of shortages
Authors: Gareth Iacobucci
Journal: BMJ (2023)

Diabetes: Doctors are told not to start new patients on GLP-1 agonists because of shortages Gareth IacobucciClinicians in England are being advised that they cannot prescribe appetite suppressants for patients with type 2 diabetes until at least the middle of next year, because of ongoing shortages.
New KRASG12C Inhibitor Demonstrates Promise
Journal: Cancer Discovery (2023)

A phase I trial of divarasib, a next-generation KRASG12C inhibitor under study to treat solid tumors, establishes the agent as safe and highlights its improved efficacy when compared with other drugs in its class. Large, randomized trials of the drug as a monotherapy and in combination with other therapies are needed to confirm these results and determine how best to use divarasib in patients with solid tumors.
Cellular and molecular waypoints along the path of T cell exhaustion
Authors: Xin Lan, Caitlin C. Zebley, Ben Youngblood
Journal: Science Immunology (2023)

Thirty years of foundational research investigating molecular and cellular mechanisms promoting T cell exhaustion are now enabling rational design of T cell-based therapies for the treatment of chronic infections and cancer. Once described as a static cell fate, it is now well appreciated that the developmental path toward exhaustion is composed of a heterogeneous pool of cells with varying degrees of effector potential that ultimately converge on a terminally differentiated state. Recent description of the developmental stages along the differentiation trajectory of T cell exhaustion has provided insight into past immunotherapeutic success and future opportunities. Here, we discuss the hallmarks of distinct developmental stages occurring along the path to T cell dysfunction and the impact of these discrete CD8+ T cell fates on cancer immunotherapy.
Sinking while you swim: A dual role for CCR7 in leukocyte migration
Authors: Hannah Donnelly, Elena Mandrou, Robert Insall
Journal: Science Immunology (2023)

The CCR7 receptor allows dendritic cells to sense the chemokine CCL19. It also depletes CCL19 from the environment by endocytosis, leading to local gradients that can steer cells accurately and robustly through tissues, even over long distances (see related Research Article by Alanko
CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration
Authors: Jonna Alanko, Mehmet Can Uçar, Nikola Canigova, Julian Stopp, Jan Schwarz, Jack Merrin, Edouard Hannezo, Michael Sixt
Journal: Science Immunology (2023)

Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein-coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.
Re: Matthew S. Ernst, Vishal Navani, J. Connor Wells, et al. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma. Eur Urol 2023;84:109–16
Authors: Jonas Saal, Viktor Grünwald, Niklas Klümper
Journal: European Urology (2023)
Examining the biological pathways underlying clinical heterogeneity in Sjogren’s syndrome: proteomic and network analysis
Authors: Joe Scott Berry, Jessica Tarn, John Casement, Pierre-Marie Duret, Lauren Scott, Karl Wood, Svein-Joar Johnsen, Gunnel Nordmark, Valérie Devauchelle-Pensec, Raphaele Seror, Benjamin Fisher, Fransesca Barone, Simon J Bowman, Michele Bombardieri, Dennis Lendrem, Renaud Felten, Jacques-Eric Gottenberg, Wan-Fai Ng
Journal: Annals of the Rheumatic Diseases (2023)

Objectives Stratification approaches are vital to address clinical heterogeneity in Sjogren’s syndrome (SS). We previously described that the Newcastle Sjogren’s Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes. Method We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST. Results Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6. Conclusions Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes.
Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults
Authors: Tianyu Zhao, Iana Markevych, Elaine Fuertes, Kees de Hoogh, Simone Accordini, Anne Boudier, Lidia Casas, Bertil Forsberg, Judith Garcia Aymerich, Marco Gnesi, Mathias Holm, Christer Janson, Deborah Jarvis, Ane Johannessen, Rudolf A. Jörres, Stefan Karrasch, Benedicte Leynaert, José Antonio Maldonado Perez, Andrei Malinovschi, Jesús Martínez-Moratalla, Lars Modig, Dennis Nowak, James Potts, Nicole Probst-Hensch, José Luis Sánchez-Ramos, Valerie Siroux, Isabel Urrutia Landa, Danielle Vienneau, Simona Villani, Bénédicte Jacquemin, Joachim Heinrich
Journal: The Lancet Regional Health - Europe (2023)

While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults.We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age.Mean ambient ozone concentrations were approximately 65 μg/m³. A one interquartile range increase of 7 μg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio.Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period.German Research Foundation.
Super-responders to anti-IL-5/anti-IL-5R are characterised by high sputum eosinophil counts at baseline
Authors: Sara Gerday, Sophie Graff, Catherine Moermans, Françoise Guissard, Virginie Paulus, Monique Henket, Renaud Louis, Florence Schleich
Journal: Thorax (2023)

Several clinical trials have demonstrated that anti-IL-5(R) biologics were able to improve lung function, asthma control and chronic oral corticosteroid exposure and reduce exacerbations among eosinophilic asthmatic patients. However, a certain variability in clinical responses to anti-IL-5(R) biologics was brought to light. Our study aimed at evaluating the role of baseline sputum eosinophils in identifying super-responders to mepolizumab and benralizumab. Our study reinforces the importance to examine sputum eosinophils in patients suffering from severe asthma before starting a biologic as it is associated with the intensity of response to mepolizumab and benralizumab.
COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study
Authors: William Hurt, Jonathan Youngs, Jonathan Ball, Jonathan Edgeworth, Philip Hopkins, David R Jenkins, Susannah Leaver, Andrea Mazzella, Síle F Molloy, Silke Schelenz, Matt P Wise, P Lewis White, Hakeem Yusuff, Duncan Wyncoll, Tihana Bicanic
Journal: Thorax (2023)

Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.
Separate and Unequal: Residential Segregation by Race and Incidence of Kidney Failure
Authors: Rudolph A. Rodriguez
Journal: Journal of the American Society of Nephrology (2023)

1Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington 2Veterans Affairs Puget Sound VA Health Care System, Seattle, Washington Correspondence: Dr. Rudolph A. Rodriguez, Puget Sound VA Health Care System, 1660 South Columbian Way, Building 1, Room 229, Seattle, WA 98119. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See related article, "Structural Racism, Historical Redlining, and Incidence of Kidney Failure in US Cities, 2012–2019," on pages 1493–1503.
Robust generation of neutralising antibodies against Omicron variants following bivalent mRNA booster vaccine in elderly people aged &gt;80 years
Authors: Helen Parry, Rachel Bruton, Grace Uwenedi, Thomas Roberts, Panagiota Sylla, Jonathan Cook, Ahmed Elzaidi, May Lau, Tamsin Drury, Alexander Bray, Soumyajit Mallick, Katie Spencer, Christopher Bentley, Graham McIlroy, Sam Scott, Nicola Logan, Jianmin Zuo, Brian Willett, Paul Moss
Journal: Journal of Infection (2023)

Dear Editor,
KLRG1 marks tumor-infiltrating CD4 T cell subsets associated with tumor progression and immunotherapy response
Authors: Casey R Ager, Mingxuan Zhang, Matthew Chaimowitz, Shruti Bansal, Somnath Tagore, Aleksandar Obradovic, Collin Jugler, Meri Rogava, Johannes C Melms, Patrick McCann, Catherine Spina, Charles G Drake, Matthew C Dallos, Benjamin Izar
Journal: Journal for ImmunoTherapy of Cancer (2023)

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios-KLRG1+ subset of tumor-infiltrating regulatory T cells was associated with tumor progression from immune equilibrium to escape and was also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumor-infiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1+ CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker discovery.